Impact of COVID-19 Lockdown on Occurrence of Acute Complications of Type 1 and Type 2 Diabetes and Overall Glycemic Management.

OBJECTIVES: The association of diabetes, and COVID-19 infection has been studied extensively; however, the occurrence of diabetic ketoacidosis (DKA) or hyperglycemic/hyperosmolar states (HHS) in adults during the lockdown has not been well characterized. In this study, we aimed to identify the impact of the lockdown on occurrence and severity of DKA/HHS admissions and glycemic management. METHODS: A retrospective chart review was conducted of patients admitted to Hamilton Health Sciences with a diagnosis of DKA or HHS from April to September 2019 (pre-lockdown) and from April to September 2020 (lockdown). Adult (≥18 years old) nonpregnant patients with a single admission in the study period were included for study. RESULTS: There were 229 admissions related to diabetes, with 171 admissions meeting the inclusion criteria (n=92 pre-lockdown, n=79 lockdown). In the lockdown group, 51.8% of the patients had type 2 diabetes mellitus, with 96.2% of admissions secondary to DKA. When comparing the 2 periods, the lockdown group trended toward higher rates of death (5.4% vs 10.1%, p=0.247) and euglycemic DKA (17.6% vs 24.4%, p=0.403). There were more new diagnoses of type 1 diabetes mellitus in the lockdown group compared with the pre-lockdown group (7.3% vs 16.7%, p=0.230). The average glycated hemoglobin was lower in the lockdown group compared with the pre-lockdown group (11.8% vs 10.4%, p=0.032). CONCLUSIONS: Overall, this study is among the first in Canada to assess the impact of the COVID-19 lockdown on admissions due to DKA and HHS. Although no significant differences were noted in severity of admissions, there was a trend toward more new diagnoses of type 1 diabetes mellitus presenting in DKA during the lockdown period.

Remission of Type 2 Diabetes Following a Short-term Intensive Intervention With Insulin Glargine, Sitagliptin, and Metformin: Results of an Open-label Randomized Parallel-Design Trial.

OBJECTIVE: The aim of the study was to evaluate remission of type 2 diabetes following a short-term intervention with insulin glargine, sitagliptin/metformin, and lifestyle approaches. RESEARCH DESIGN AND METHODS: In this open multicenter trial, 102 patients with type 2 diabetes were randomized to 1) a 12-week intervention with sitagliptin/metformin, insulin glargine, and lifestyle therapy or 2) control group. Participants with HbA1c <7.3% (<56 mmol/mol) at 12 weeks were asked to stop diabetes medications and were followed for evidence of relapse over 52 weeks. Diabetes relapse criteria included HbA1c ≥6.5% (≥48 mmol/mol), ≥50% of capillary glucose readings >10 mmol/L over 1 week, and reinitiation of diabetes medications with or without abnormal fasting plasma glucose (FPG) or 2-h plasma glucose on an oral glucose tolerance test (OGTT). Time-to-relapse analysis was conducted to compare the treatment groups with (primary analysis) and without (supplementary analysis) FPG/OGTT relapse criteria. RESULTS: With the FPG/OGTT relapse criteria included, the hazard ratio (HR) of relapse was 0.72 (95% CI 0.47-1.10) in the intervention group compared with the control group (primary analysis), and the number of participants remaining in remission was not significantly different between treatment groups at 24, 36, 48, and 64 weeks. In the supplementary analyses without these criteria, HR of relapse was 0.60 (95% CI 0.39-0.95), and the number of participants remaining in remission was significantly higher (26 vs. 10%) in the intervention group at 36 weeks. CONCLUSIONS: Although our primary outcome was not statistically significant, the tested approach deserves further study with further optimization of its components.

Canadian national hypoparathyroidism registry: an overview of hypoparathyroidism in Canada.

PURPOSE: To evaluate the epidemiology, presentation and management of hypoparathyroidism in Canada. Hypoparathyroidism is associated with significant morbidity and poor quality of life. We present baseline results from the Canadian National Hypoparathyroidism Registry, a prospective observational study evaluating hypoparathyroidism in Canada. METHODS: Our study enrolled 130 patients with hypoparathyroidism. Patients were followed every 6 months with clinical and lab assessments. We present baseline data in this manuscript. RESULTS: Seventy percent (91/130) of patients had postsurgical hypoparathyroidism, 30% (39/130) of patients had nonsurgical hypoparathyroidism due to autoimmune, genetic or idiopathic causes, and a molecular diagnosis was confirmed in 11 of these 39 patients. Pseudohypoparathyroidism was confirmed in 4/39 patients, DiGeorge syndrome in 2/39 patients, Barakat syndrome with a mutation in the GATA3 gene in 1/39, and activating mutations of the CASR gene in 3/39 patients with nonsurgical hypoparathyroidism. Renal complications with nephrocalcinosis or nephrolithiasis were present in 27% (14/52) of patients with postsurgical disease and 17% (4/24) of patients with nonsurgical hypoparathyroidism. Basal ganglia calcification was noted on imaging in 15% (n = 5/34) of patients with postsurgical hypoparathyroidism and 37% (n = 7/19) of patients with nonsurgical hypoparathyroidism. CONCLUSIONS: Hypercalciuria was more commonly seen in those with renal complications of nephrocalcinosis, nephrolithiasis or CKD, and hyperphosphatemia was more commonly seen in those with basal ganglia calcification. Hospitalization occurred in 28% of those with postsurgical hypoparathyroidism and 46% of those with nonsurgical hypoparathyroidism. Hypoparathyroidism is associated with significant morbidity. Effective strategies to reduce the short-and long-term complications of hypoparathyroidism need to be developed and evaluated.

The effects of rosiglitazone on inflammatory biomarkers and adipokines in diabetic, hypertensive patients.

OBJECTIVE: To compare the effects of a 12-week treatment course of a rosiglitazone-based versus a metformin- or glyburide-based strategy on inflammatory biomarkers and adipokine levels in hypertensive, type 2 diabetes patients. METHODS: One hundred three treatment-naive patients or patients on monotherapy with either metformin or glyburide, and a hemoglobin A1C (A1C) ≥7.5%, were randomly assigned to either rosiglitazone add-on (4 mg/day ± titration to 8 mg/day) or a combination of metformin (250 mg twice per day [BID] titrated to 500 BID if A1C ≥7.5% and ≤8.0%; 500 mg BID titrated to 1 g BID if A1C >8.0%) and glyburide (2.5 mg BID titrated to 5 mg BID if A1C ≥7.5% and ≤8.0%; 5 mg BID titrated to 10 mg BID if A1C >8.0%). RESULTS: Rosiglitazone add-on produced significantly greater reductions in high-sensitivity C-reactive protein (2.1 mg/L to 0.9 mg/L) and increases in adiponectin (8.7 mg/mL to 14.8 mg/mL) levels compared with metformin/glyburide (both P<0.005). At close-out, all patients had improved fasting plasma glucose and A1C levels (8.5% to 7.4% and 8.8% to 7.1% for rosiglitazone add-on and metformin-glyburide, respectively [P<0.001 for both arms]) relative to the corresponding baseline values. CONCLUSIONS: The present study demonstrated that in hypertensive, diabetic subjects, a rosiglitazone-based treatment strategy results in favourable changes in inflammatory biomarkers compared with metformin/glyburide.

Patient age, ethnicity, medical history, and risk factor profile, but not drug insurance coverage, predict successful attainment of glycemic targets: Time 2 Do More Quality Enhancement Research Initiative (T2DM QUERI).

OBJECTIVE: To identify factors in patients with type 2 diabetes and A1C >7.0% associated with attainment of A1C ≤ 7.0%. RESEARCH DESIGN AND METHODS: We used a prospective registry of 5,280 Canadian patients in primary care settings enrolled in a 12-month glycemic pharmacotherapy optimization strategy based on national guidelines. RESULTS: At close out, median A1C was 7.1% (vs. 7.8% at baseline) with 48% of subjects achieving A1C ≤ 7.0% (P < 0.0001). Older patients of Asian or black origin, those with longer diabetes duration, those with lower baseline A1C, BMI, LDL cholesterol, and blood pressure, and those on angiotensin receptor blockers and a lower number of antihyperglycemic agents, were more likely to achieve A1C ≤ 7.0% at some point during the study (all P < 0.0235). Access to private versus public drug coverage did not impact glycemic target realization. CONCLUSIONS: Patient demography, cardiometabolic health, and ongoing pharmacotherapy, but not access to private drug insurance coverage, contribute to the care gap in type 2 diabetes.

Treatment gaps in the management of cardiovascular risk factors in patients with type 2 diabetes in Canada.

OBJECTIVES: To evaluate vascular protection treatment patterns and attainment of the 2003 Canadian Diabetes Association's recommended targets in ambulatory patients with type 2 diabetes. METHODS: Between 2005 and 2006, 3002 outpatients with type 2 diabetes were enrolled by 229 primary health care settings across Canada. Baseline characteristics, therapeutic regimens and treatment success - defined as the achievement of a blood pressure (BP) of 13080 mmHg or lower, glycosylated hemoglobin (A1C) of 7% or lower, low-density lipoprotein cholesterol (LDL-C) lower than 2.5 mmolL and total cholesterolhigh-density lipoprotein cholesterol ratio lower than 4.0 - are reported. RESULTS: Overall, 46% of individuals had a BP that was above the Canadian Diabetes Association's recommended target. Of these, 11% were untreated, 28% were receiving monotherapy, 38% were not receiving an angiotensin-converting enzyme inhibitor and 16% were not receiving either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Optimal A1C levels were achieved in 53% of patients. Of those who did not attain A1C targets, 3% were not on glucose- lowering pharmacotherapy and 27% were receiving monotherapy. A total of 74% of patients were treated with statins. Overall, 64% and 62%, respectively, met the target LDL-C and the target total cholesterolhigh-density lipoprotein cholesterol ratio. Statins were not prescribed to 43% of patients with LDL-C above target. Antiplatelet therapy was implemented in 81% of patients. In total, 21% achieved the combined targets for BP, A1C and LDL-C. INTERPRETATION: A substantial proportion of patients did not achieve guideline-recommended targets and were not receiving evidence- based therapy for vascular protection two years after publication of the Canadian guidelines. More research is warranted, and novel and effective strategies must be tested and implemented to correct this ongoing treatment gap.

Effects of ezetimibe add-on to statin therapy on adipokine production in patients with metabolic syndrome and stable vascular disease.

The aim of this study was to determine whether the addition of ezetimibe to ongoing statin therapy in patients with atherosclerosis and metabolic syndrome would favorably affect levels of inflammatory markers and adipokines. Individuals with the metabolic syndrome exhibit higher levels of inflammatory biomarkers and adipokines, which have been implicated in the pathobiology of cardiovascular risk. The impact of the addition of ezetimibe to statin therapy on these proinflammatory mediators is unclear. Fifty patients with metabolic syndrome and concomitant vascular disease receiving stable statin monotherapy, with low-density lipoprotein cholesterol (LDL-C) levels >77.4 mg/dL (>2.0 mM), were treated with ezetimibe 10 mg per day for 12 weeks. The primary study end point was the % change in adiponectin levels from baseline to 12 weeks. Secondary study end points included % changes in the levels of other circulating inflammatory markers, adipokines, and plasma lipids. The addition of ezetimibe to statin therapy resulted in a significant reduction in total cholesterol and LDL-C and the ratio of total cholesterol to high-density lipoprotein cholesterol. However, ezetimibe add-on treatment had no effect on the primary outcome of plasma adiponectin or on any of the secondary outcomes, including leptin, hsCRP, tumor necrosis factor-α, or interleukin-6 concentrations. These observations remained unchanged after adjusting for body mass index and for background statin used. The addition of ezetimibe to stable statin therapy in patients with vascular disease and metabolic syndrome, who were not at guideline recommended LDL-C levels, did not alter adipokine levels after 12 weeks. Short-term add-on with ezetimibe may not be associated with additional inflammatory benefits beyond improvements in cholesterol homeostasis.

Role of renin-angiotensin system blockade in patients with diabetes mellitus.

The investigators review the evidence of the potential role of renin-angiotensin system (RAS) blockers in delaying or preventing the onset and progression of diabetes mellitus (DM) and cardiovascular disease and the suggested mechanisms by which these agents exert their favorable metabolic and cardiovascular effects. Data from clinical trials suggest that RAS blockade not only reduces cardiovascular risk in patients with DM but also may prevent or delay DM onset in at-risk subjects. These observations set the stage for further studies evaluating the risk for developing DM as a primary end point: the Diabetes Reduction Approaches With Ramipril And Rosiglitazone Medications (DREAM) trial, in which ramipril significantly increased regression to normoglycemia (although it did not reduce the primary end point of new-onset DM or death), and the ongoing Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, the only DM prevention trial also powered to evaluate whether a reduced risk for DM is associated with a reduction in cardiovascular disease events. In conclusion, overwhelming evidence suggests that the RAS plays an important role in the pathogenesis of DM and its associated cardiovascular risks.

Statin effects on LDL and HDL cholesterol in South Asian and white populations.

Inasmuch as statins appear to exhibit altered efficacy in some Asian populations (predominantly East Asian), current lipid guidelines recommend the use of lower statin doses in all Asians. Whether this should also apply to South Asians, a population at high risk for coronary heart disease, remains unclear. The authors evaluated the lipid-modifying effects of statins in South Asian and white patients with established coronary heart disease. Atorvastatin (median dose=20 mg/d in both groups) produced similar decreases in low-density lipoprotein cholesterol (LDL-c) in South Asian (43%) and white (41%) patients and raised high-density lipoprotein cholesterol (HDL-c) by 19% in South Asians and by 12% in whites. Simvastatin (median dose=20 mg/d in both groups) reduced LDL-c by 35% in South Asians and by 37% in whites while raising HDL-c by 12% in both groups. Using a multiple linear regression model (atorvastatin equivalent), the expected decrease in LDL-c for 10 mg atorvastatin and 20 mg atorvastatin was similar between the groups. Results indicate that atorvastatin and simvastatin, at commonly prescribed doses, modulate LDL-c and HDL-c levels to a similar degree in both South Asians and whites with documented coronary heart disease. These findings suggest that South Asian patients may be treated with atorvastatin and simvastatin at doses typically applied to white patients.

Efficacy and safety of ursodeoxycholic acid in primary, type IIa or IIb hypercholesterolemia: a multicenter, randomized, double-blind clinical trial.

BACKGROUND: Ursodeoxycholic acid (UDCA) is a therapeutic bile acid used in dissolution of gallstones and treatment of several cholestatic liver diseases. Results obtained from primary biliary cirrhosis patients treated with UDCA suggested that this agent exerts significant cholesterol-lowering effects and justifies evaluation in primary hypercholesterolemic patients without liver disease. Purpose of this study was to determine whether UDCA had potential to be an effective, safe cholesterol-lowering agent in primary type IIa or IIb hypercholesterolemia. METHODS: This was a multicenter randomized, double blind, placebo-controlled trial. After a 6-week placebo lead-in period during which two qualifying lipid profiles were obtained, patients with a mean serum LDL-cholesterol (LDL-C) between 130 and 190mg/dL, triglycerides <400mg/dL and HDL-cholesterol >30mg/dL were randomized to UDCA or matching placebo for 24 weeks. RESULTS: Seven sites screened 200 patients with 134 patients meeting the entry criteria who were randomized to the two treatments. There were 125 patients meeting the efficacy evaluation criteria, 57 on UDCA and 68 on placebo. LDL-C change from weeks 0 to 24 showed no significant difference between groups. No significant differences in changes for total cholesterol, HDL-cholesterol and triglycerides were observed. Both groups had similar adverse event profiles. CONCLUSIONS: UDCA did not show intrinsic cholesterol-lowering properties and therefore is not a useful therapy in treating type IIa or type IIb hypercholesterolemic patients. UDCA was confirmed as a well tolerated and safe drug in this population.

A randomized, controlled trial of the effects of rosiglitazone on adipokines, and inflammatory and fibrinolytic markers in diabetic patients: study design and protocol.

BACKGROUND: Although rosiglitazone may offer vascular benefits beyond lowering glucose, recently, concern has been raised that this drug may paradoxically increase cardiovascular risk. OBJECTIVE: To assess the effects of rosiglitazone compared with standard oral hypoglycemic therapies on adipokines, and inflammatory and fibrinolytic markers in subjects with type 2 diabetes. METHODS: A 12-week, randomized, open-label, parallel-group study will be conducted on 100 type 2 diabetic subjects with suboptimal glycemic control (glycosylated hemoglobin 0.075 or greater) despite management with lifestyle alone (drug-naive) or with monotherapy (either metformin or sulfonylurea). Drug-naive patients will be randomly assigned to receive either rosiglitazone (4 mg/day to 8 mg/day) or metformin (500 mg/day to 2000 mg/day). Patients on pre-existing monotherapy will be randomly assigned to the addition of rosiglitazone (4 mg/day to 8 mg/day), or to either metformin (500 mg/day to 2000 mg/day) or glyburide (5 mg/day to 20 mg/day) (depending on background treatment). The primary end point of the study is the change in adiponectin level (from baseline to 12 weeks) in the rosiglitazone versus metformin or sulfonylurea arms. Secondary end points include changes in leptin, high-sensitivity C-reactive protein, interleukin-6, tumour necrosis factor-alpha, matrix metalloproteinase-9, vascular cell adhesion molecule-1, plasminogen activator inhibitor type 1, insulin sensitivity, glycosylated hemoglobin and lipid levels. Additionally, all patients will be required to be treated with an inhibitor of the renin-angiotensin system, namely an angiotensin receptor antagonist, as per national diabetes treatment guidelines, to a target systolic blood pressure of less than 130 mmHg and a diastolic blood pressure of less than 80 mmHg, or for the optimal suppression of microalbuminuria.

Recommendations for management of dyslipidemia in high cardiovascular risk patients.

Overwhelming evidence supports a causal relationship between elevated levels of plasma cholesterol, particularly low-density lipoprotein cholesterol, and increased risk of coronary artery disease, which remains the leading cause of death and morbidity worldwide. Low-density lipoprotein cholesterol lowering has been the main goal of therapy, and clinical trial results from recently published studies of intensive statin therapy confirm the benefits of more aggressive lipid-lowering targets, particularly in subjects at high risk for cardiovascular events. This management update will focus on the implications of risk reduction in patients at high cardiovascular risk, and will provide practical steps to help further risk stratify these patients and help them reach their target goals.

Avaliação da variação do pH salivar através da utilização de gomas de mascar contendo xilitol / Evaluation of saliva pH variation through the use of xilitol chewing gums

O objetivo desse trabalho foi avaliar o xilitol contido em uma goma de mascar mediante a variação do pH salivar, comparando-o com a clorexidina. Foram selecionadas 19 crianças que não possuíam clinicamente atividade de cárie. Utilizou-se: xilitol (grupo teste). clorexidina (controle positivo) e sacarose (controle negativo). Coletou-se a saliva de cada criança e foram medidos os pH iniciais e após o uso de cada substância (pH final). Foi concluído que a ação do xilitol na elevação do pH salivar pode ser considerada um efeito anticariogênico, assim como a clorexidina.